A5068320484- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Bladder and Urothelial Cancer Treatments
- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- Ferroptosis and cancer prognosis
- Brain Metastases and Treatment
- Cytomegalovirus and herpesvirus research
- Single-cell and spatial transcriptomics
- Radiopharmaceutical Chemistry and Applications
- Mycobacterium research and diagnosis
- Epigenetics and DNA Methylation
- Advanced biosensing and bioanalysis techniques
- Nanoplatforms for cancer theranostics
- Computational Drug Discovery Methods
- T-cell and B-cell Immunology
- Lung Cancer Research Studies
- Bioinformatics and Genomic Networks
- Urinary Bladder and Prostate Research
- Nanoparticle-Based Drug Delivery
- Renal and related cancers
- Testicular diseases and treatments
- Genetic Associations and Epidemiology
- Mass Spectrometry Techniques and Applications
University of North Carolina at Chapel Hill
2016-2023
Uber AI (United States)
2022-2023
University of North Carolina Health Care
2019-2022
UNC Lineberger Comprehensive Cancer Center
2016-2022
Communities In Schools of Orange County
2017
Segeberger Kliniken
2016
We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These exhibited high aneuploidy a paucity somatic mutations. Somatic mutation only three genes achieved significance—KIT, KRAS, NRAS—exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes TGCT: seminoma, embryonal carcinoma, yolk...
For the past decade, cancer genomic studies have focused on mutations leading to splice-site disruption, overlooking those having splice-creating potential. Here, we applied a bioinformatic tool, MiSplice, for large-scale discovery of splice-site-creating (SCMs) across 8,656 TCGA tumors. We report 1,964 originally mis-annotated clear evidence creating alternative splice junctions. TP53 and GATA3 26 18 SCMs, respectively, ATRX has 5 from lower-grade gliomas. Mutations in 11 genes, including...
We report the discovery of a claudin-low molecular subtype high-grade bladder cancer that shares characteristics with homonymous breast cancer. Claudin-low tumors were enriched for multiple genetic features including increased rates RB1, EP300, and NCOR1 mutations; frequency EGFR amplification; decreased FGFR3, ELF3, KDM6A PPARG amplification. While showed highest expression immune gene signatures, they also demonstrated patterns consistent those observed in active immunosuppression. This...
Abstract High-grade urothelial cancer contains intrinsic molecular subtypes that exhibit differences in underlying tumor biology and can be divided into luminal-like basal-like subtypes. We describe here the first subtype-specific murine models of bladder show Upk3a-CreERT2; Trp53L/L; PtenL/L; Rosa26LSL-Luc (UPPL, luminal-like) BBN (basal-like) tumors are more faithful to human than widely used MB49 cells. Following engraftment immunocompetent C57BL/6 mice, were responsive PD-1 inhibition...
Measures of the adaptive immune response have prognostic and predictive associations in melanoma other cancer types. Specifically, intratumoral T cell density function considerable value skin cutaneous (SKCM). Less is known about significance tumor-infiltrating B cells SKCM. Our goal was to understand phenotypic subsets SKCM using RNA sequencing. We used our previously published algorithm, V'DJer, assemble receptor (BCR) repertoires estimate diversity from short-read sequencing (RNA-seq)....
Current tumor neoantigen calling algorithms primarily rely on epitope/major histocompatibility complex (MHC) binding affinity predictions to rank and select for potential epitope targets. These do not predict immunogenicity using approaches modeled from tumor-specific antigen data. Here, we describe peptide-intrinsic biochemical features associated with minor mismatch present a gradient boosting algorithm predicting immunogenicity. This was validated in two murine models demonstrated the...
The human leukocyte antigen (HLA) system is a genomic region involved in regulating the immune by encoding cell membrane major histocompatibility complex (MHC) proteins that are responsible for self-recognition. Understanding variation this provides important insights into autoimmune disorders, disease susceptibility, oncological immunotherapy, regenerative medicine, transplant rejection, and toxicogenomics. Traditional approaches to HLA typing low throughput, target only few genes, labor...
Abstract Purpose: Despite promising advances in breast cancer immunotherapy, augmenting T-cell infiltration has remained a significant challenge. Although neither individual vaccines nor immune checkpoint blockade (ICB) have had broad success as monotherapies, we hypothesized that targeted vaccination against an oncogenic driver combination with ICB could direct and enable antitumor immunity advanced cancers. Experimental Design: Our models of HER2+ exhibit molecular signatures are...
Splice variant neoantigens are a potential source of tumor-specific antigen (TSA) that shared between patients in variety cancers, including acute myeloid leukemia. Current tools for genomic prediction splice demonstrate promise. However, many have not been well validated with simulated and/or wet lab approaches, no studies published presented targeted immunopeptidome mass spectrometry approach designed specifically identification predicted neoantigens.In this study, we describe NeoSplice,...
Abstract Motivation Elimination of cancer cells by T is a critical mechanism anti-tumor immunity and immunotherapy response. recognize engagement cell receptors with peptide epitopes presented major histocompatibility complex molecules on the surface. Peptide can be derived from antigen proteins coded for multiple genomic sources. Bioinformatics tools used to identify tumor-specific via analysis DNA RNA-sequencing data have largely focused somatic variants, though smaller number evaluated...
Claudin-low molecular subtypes have been identified in breast and bladder cancers are characterized by low expression of claudins, enrichment for epithelial-to-mesenchymal transition (EMT), tumor-initiating cell (TIC) features. We evaluated whether the claudin-low subtype also exists gastric cancer.Four hundred fifteen tumors from The Cancer Genome Atlas (TCGA) cancer mRNA data set were clustered on claudin, EMT, TIC gene sets to identify tumors. derived a 24-gene predictor that classifies...
Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with complex traits and diseases. However, most them are located in the non-protein coding regions, therefore it is challenging to hypothesize functions these non-coding GWAS variants. Recent large efforts such as ENCODE Roadmap Epigenomics projects predicted a number regulatory elements. target genes elements remain largely unknown. Chromatin conformation capture based technologies Hi-C can...
Background Triple negative breast cancer (TNBC) is an aggressive variant of that lacks the expression estrogen and progesterone receptors (ER PR) HER2. Nearly 50% patients with advanced TNBC will develop brain metastases (BrM), commonly progressive extracranial disease. Immunotherapy has shown promise in treatment TNBC; however, immune contexture BrM remains largely unknown. We conducted a comprehensive analysis matched primary tumors to characterize genomic landscape inform development...
Tandem mass spectrometry (MS/MS) is a highly sensitive and selective method for the detection of tumor-associated peptide antigens. These short, nontryptic sequences may lack basic residues, resulting in formation predominantly [peptide + H]+ ions electrospray. singly charged tend to undergo inefficient dissociation, leading issues sequence determination. Addition alkali metal salts electrospray solvent can drive H metal]2+ that have enhanced dissociation characteristics relative ions. Both...
Abstract Motivation Elimination of cancer cells by T is a critical mechanism anti-tumor immunity and immunotherapy response. recognize engagement cell receptors with peptide epitopes presented major histocompatibility complex (MHC) molecules on the surface. Peptide can be derived from antigen proteins coded for multiple genomic sources. Bioinformatics tools used to identify tumor-specific via analysis DNA RNA sequencing data have largely focused somatic variants, though smaller number...
Abstract Introduction: High-grade, muscle-invasive bladder cancer has recently been shown to harbor intrinsic molecular subtypes with distinct biologic features. Current murine models of cancer, including the prominent carcinogen induced model MB49, do not account for subtype specific characteristics, leaving a gap in available tools understanding differences cancer. We have developed and validated immunocompetent, we used these assess differential responses immune checkpoint inhibition....
Abstract Rationale: High-grade urothelial carcinoma of the bladder is a heterogeneous disease, with molecular subtypes characterized by distinct tumor biologies and prognoses. Our group others have described basal luminal subtypes, we now report on discovery claudin-low subtype, all which resemble analogous in breast cancer. Methods: We analyzed mRNA sequencing whole exome data for The Cancer Genome Atlas (TCGA) tumors collected at UNC. performed unsupervised hierarchical clustering relative...